Substituted azetidinones of the following general formula ##STR2## have been found to be useful as anti-inflammatory and anti-degenerative agents. Their utility in treating human leukocyte elastase mediated diseases and their method of preparation is disclosed in EPO 337,549 published Oct. 18, 1989, which reference is hereby incorporated by reference.
The prior art comprises:
Tetrahedron Letters pp. 1977 (1977) which discloses intermolecular dehydration reaction occuring between alcohols and acidic portion of the subject molecule on treatment with diethyl azodicarboxylate and triphenyl phosphine under neutral conditions [i.e., the Mitsunobu Reaction]; Tetrahedron Letters Vol. 30 (13) pp. 1657-60 (1989) which discloses the use of chiral catalysts;
Chem. Ber. Vol. 117 pp. 2988-2997 (1984); Bull. Chem. Soc. Jpn. Vol. 56 p. 2762 (1983); and Org. Syn. Coll. Vol. 5 pp. 251 which disclose benzofuran synthesis via the Perkin reaction.
The instant invention represents an important advance over the art. For example, Applicants have suprisingly achieved excellent control of absolute stereo chemistry in a Mitsunobu azide displacement on an electron rich benzylic alcohol.